Rare genetic diseases and syndromes may appear with unique features in some patients. In genetically-solved cases, this situation indicates a phenotypic expansion of the syndrome with additional features (i.e. the disease-associated gene gives rise to unusual clinical presentation). However, this situation can also hide a multilocus pathogenic variation that cannot be solved genetically except by a massive sequencing approach, such as exome sequencing. Here we describe the case of a child with bilateral radial aplasia, transient thrombocytopenia and anemia, cow's milk intolerance, hypospadias, facial dysmorphism, mild hypothyroidism and umbilical and inguinal hernia. Bilaterally absent radius, presence of thumbs and low platelet count are pathognomonic of thrombocytopenia absent radius (TAR) syndrome, but the child also showed other features beyond those reported in the literature. Since various diseases resembling the proband's phenotype required differential diagnosis, clinical exome sequencing was performed. The results showed compound heterozygous mutations in the RBM8A gene, confirming the suspicion of TAR syndrome. A truncating heterozygous variant in the DUOX2 gene, known to be associated with transient thyroid dyshormonogenesis type 6 (TDH6), was also detected and may explain the proband's mild hypothyroidism.

中文翻译：

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尿道下裂扩大了无radius骨综合征的血小板减少症的表型。

在某些患者中，罕见的遗传病和综合症可能表现出独特的特征。在遗传学解决的病例中，这种情况表明该综合征具有其他特征的表型扩展（即与疾病相关的基因导致异常的临床表现）。但是，这种情况也可能隐藏了多基因座致病变异，除非通过大规模测序方法（例如外显子组测序）才能通过遗传手段解决。在这里，我们描述了一个患双侧radial骨发育不全，短暂性血小板减少症和贫血，牛奶耐受性差，尿道下裂，面部畸形，轻度甲状腺功能减退症以及脐带和腹股沟疝的儿童的病例。radius骨双侧不存在，拇指的存在和血小板计数低是血小板减少症radius骨（TAR）综合征的病理学特征，但是这个孩子还表现出了文献报道以外的其他特征。由于各种与先证者表型相似的疾病需要鉴别诊断，因此进行了临床外显子组测序。结果表明，RBM8A基因存在复合杂合突变，证实了TAR综合征的可能。还检测到DUOX2基因中的一个截断的杂合变异体，该变异体与短暂性甲状腺功能失调发生类型6（TDH6）有关，可能解释了先证者的轻度甲状腺功能低下。